Prophylactic intranasal IFN-α cuts COVID-19 incidence in cancer patients

Prophylactic interferon-alpha (IFN-α) administered intranasally slashed the incidence of COVID-19 by almost half in a cohort of cancer patients in the C-SMART study.

“By the end of the treatment period, [there were] around 14 percent of participants [in the placebo group] who were COVID-19-positive,” said Dr Michelle Yong from the Peter MacCallum Cancer Centre, Melbourne, Australia, who presented the findings at ESCMID Global 2024.

Looking at the IFN-α group, there was a significantly lower incidence of COVID-19 (8.3 percent) and widening of incidence curves between treatment arms over time, Yong continued. A comparison between the IFN-α and placebo arms generated a hazard ratio (HR) of 0.55 (95 percent confidence interval [CI], 0.32–0.97; p=0.04).

In the forest plot of the ITT cohort, the relative risk (RR) of COVID-19 with IFN-α was 0.60 (95 percent credible interval [CrI], 0.33–0.97). Age <65 years was protective (RR, 0.48), as were female sex (RR, 0.44) and any COVID-19 vaccine (RR, 0.50), Yong said.

She further noted that the results were even stronger in the per-protocol (PP; n=389) cohort. The relative risk of COVID-19 with IFN-α was 0.50 (95 percent CrI, 0.26–0.84). Age <65 years, female sex, and any COVID-19 vaccine remained protective (RRs, 0.36, 0.36, and 0,49, respectively), with the addition of solid tumour cancers (RR, 0.39). [ESCMID Global 2024, abstract O0522]

In the PP population, the cumulative incidence of COVID-19 remained lower with IFN-α vs placebo (7.7 percent vs 16 percent; HR, 0.46, 95 percent CI, 0.26–0.82; p=0.008).

IFN-α has biological activities, including antiviral, antiproliferative, and immunomodulatory effects, noted Yong. “There are [studies] of IFN-α nasal application used as post-exposure prophylaxis in household contacts. When given within 48 hours, [intranasal IFN-α] reduced seasonal influenza in a nonimmune compromised population. It has also been used with rhinovirus.”

“[Therefore,] we hypothesized that IFN-α might affect COVID-19 or respiratory viral epidemiology,” she pointed out.

Yong and her team evaluated 433 adults (median age 62 years, 51 percent women) with solid tumours or haematological malignancies (ITT population). Participants were randomized 1:1 to receive either IFN-α 40,000 IU daily via nasal administration or matching placebo (0.9% saline) for 90 days.

Eleven percent of the overall population were diagnosed with COVID-19. Overall, only 5 percent had other respiratory viruses, the most common being picornavirus and seasonal coronavirus.

A tenth of participants overall reported adverse events (AEs), but these were mostly mild to moderate. Nasal bleeding was an AE of special interest, and all cases were observed in the IFN-α arm. “Most of the causality of all the AEs, whether they are cancer-related, hospitalizations for surgery, or disease progression, were not related to the intervention,” said Yong.

Takeaways

“IFN-α 40,000 IU delivered as a nasal spray daily significantly reduced the incidence of COVID-19 by 40–50 percent, with a number needed to treat of 16. This was a well-tolerated prophylactic strategy,” said Yong.

“This is novel and clinically useful for short periods in a high-risk immunocompromised population, such as patients having a pretransplant period and those having chemotherapy wherein getting infections significantly impacts therapy,” she continued.

When asked how IFN-α fares when compared against COVID-19 vaccines, Yong was quick to point out that a comparison with a vaccine cannot be made. “Along the course of the trial, vaccines became more widespread. We factored that into the post analysis. That was not a head-to-head comparison. We do not feel that that’s where it’s going to be placed – IFN-α would be an addition to current COVID-19 preventive measures.”

Yong added that they’d be pursuing further investigation and look into other respiratory viral events (eg, respiratory syncytial virus) given the low incidence in the study.